(Investigator?s Abstract): With the near completion of the human genome project the emphasis in biological research will undoubtedly shift from a gene-by-gene analysis to more global studies of gene expression. Funds are being requested for the purchase of the Affymetrix cDNA microarray system in order to introduce this technology to cell and molecular biology research projects ongoing in the Lerner Research Institute and to complement the Affymetrix GeneChip oligonucleotide array system already available as a core service. The acquisition of this state-of-the art inicroarray system will impact on many researci projects currently underway in the Lerner Research Institute. The system combines several unique features that will empower researchers throughout the Institute to extend their gene expression profiling in a variety of different cellular systems. At present the Affymetrix oligonucleotide arrays are being used in a discovery mode to identify patterns of gene expression in certain cell types and tissues as well as to make highly quantitative comparisons in gene expression levels between paired samples. The availability of a cDNA microarray system would complement the GeneChip effort by allowing individual researchers to make custom arrays either using genes entirely selected from the databases or from a combination of database and GeneChip predictions. The microarray system will be housed in the gene expression core facility and will be operated and maintained by core staff ensuring the production of high quality custom designed arrays. Researchers at the Cleveland Clinic are in a unique position, in that close collaboration with clinical personnel allows access to a wide variety of patient material and identification of many interesting and clinically relevant diseases and syndromes. The ability to analyze global gene expression in clinically relevant disorders would aid significantly in identification of genes involved in a wide variety of medical conditions and possibly suggest therapeutic targets. The ability to rapidly identify genetic changes associated with disease states will also considerably further our understanding of the causative mechanisms involved. The capability to generate custom cDNA arrays will not only enhance ongoing research projects but will inspire the development of new avenues in the analysis of biological systems from many investigators currently not able to pursue specific high throughput gene profiling in their experimental systems.